Single cell gene correlation with neuropathology markers
C9
In excitatory neurons, correlations between cell-type markers and significantly deregulated genes in FTLD-C9 highlighted a consistent association with STMN2 expression, a gene central to axonal maintenance.
Across several RORB-characterized excitatory subtypes, including RORB/FOXO1, RORB/LRRK1 and RORB/ADGRL4, and PCP4/NXPH2, strong negative correlations with STMN2 were observed. Among these, the RORB/FOXO1 gene C9orf72 correlation with STMN2 (ρ = −0.99, p = 0,016), the RORB/LRRK1 genes STMN2 (ρ = −0.85, p = 0,0016), NPTX2 (ρ = −0.73, p = 0,013), C9orf72 (ρ = -0,85, p = 0,0016), SPP1 (ρ = −0.8, p = 0,005), the RORB/ADGRL4 C9orf72(ρ = -0,66, p = 0,0308), STMN2(ρ = -0,74, p = 0,011) and PCP4/NXPH2 STMN2 (ρ =-0.84, p = 0.001).
THEMIS- characterized cells also shown genes with STMN2 marker correlation. THEMIS/NR4A2 STMN2 (ρ =-0.65, p = 0.029), THEMIS/TMEM233 C9orf72(ρ =-0.66, p = 0.025), NPTX2(ρ =-0.63, p = 0.034) and STMN2(ρ =-0.75, p = 0.01), TLE4/MEGF11 STMN2(ρ =-0.65, p = 0.028) and TLE4/SEMA3D C9orf72(ρ =0.61, p = 0.046) and CX3CR1(ρ =0.82, p = 0.0016) .
These findings indicate that, although excitatory neuron proportions defined by RORB expression do not differ between FTLD-C9 and controls, their association with STMN2 expression reflects a dynamic remodeling of excitatory circuits along disease progression, suggesting that excitatory neuronal dysfunction is intimately linked to STMN2-associated pathology.
Only THEMIS/TMEM233 STMN2 expression shown correlation with pTDP43 marker (ρ = 0.809, p = 0.021). In non-neuronal populations, significant correlations with STMN2 expression were detected in oligodendrocytes. In it both C9orf72 (ρ = −0.64, p = 0.03) and STMN2 (ρ = −0.63, p = 0.04) were negatively correlated with STMN2, further reinforcing the presence of interactions in STMN2-dependent processes.
Code
library(readxl)library(dplyr)library(DT)# ============================================================# LOAD DATA# ============================================================file_path <-"/media/jaumatell/datos/URI/BAYESPRISM_12_3/RESULTS_ORDERED/6. GENES OF INTERST CORRELATION/C9_genes_correlation_allCovs.csv"filtered <-read.csv(file_path)# ============================================================# CLEAN COLUMN NAMES IF NEEDED# Some sheets have "NA." or "rho" in first column.# Keep only meaningful columns: Cell, Gene, Spearman, p_value.# ============================================================# Try to detect the first unnamed column (if present)first_col <-colnames(filtered)[1]if (first_col %in%c("NA.", "rho", "rho1", "", NA)) { filtered <- filtered %>%select(-1)}# ============================================================# FILTERABLE HTML TABLE FOR QUARTO# ============================================================datatable( filtered,filter ="top",options =list(scrollX =TRUE,pageLength =25,dom ="frtip"# no download buttons ))
In excitatory neurons, correlations with TDP-43 burden revealed strong and consistent associations with STMN2 expression and TDP43b. The RORB/ADGRL4 subtype showed SPP1 (-0.81, 0.0078) and CX3CR1 (-0.79, 0.01) negatively correlating with TDP43 burden. RORB/LRRK1 subtype showed one of the most pronounced effects in correlation with TDP43b, with genes NPTX2 (ρ = −0.78, p = 0,017), STMN2 (ρ = −0.8, p = 0,013), C9orf72 (ρ = −0,8, p = 0,013), SPP1(ρ = −0.73, p = 0,031) and CX3CR1 (ρ = −0.71, p = 0,031) significativly negatively correlated.
Other excitatory subtypes also showed significant negative correlations with TDP43b, including CUX2/RASGRF2 with NPTX2 (ρ = −0.7, p = 0.043) and RORB/POU3F2 with NPTX2 (ρ = −0.75 , p = 0.025) and CX3CR1 (ρ = −0.8 , p = 0.013).
Additionaly neuropathology marker STMN2 in CUX2/RORB also correlated negatively with NPTX2expression (ρ = −0.80 , p = 0.016). Together, these findings point to a robust inverse association between excitatory neuron signatures and STMN2 levels in the context of TDP-43 pathology, suggesting a central role of excitatory neuronal dysfunction in linking STMN2 downregulation with TDP-43 accumulation.
In non-neuronal populations, strong correlations with STMN2 were also observed. In TLE4/CCBE1 cells STMN2 pathology showed negative correlation, with C9orf72 (ρ = -0.76, p = 0.025), also the astrocyte GFAP - correlated negatively with C9orf72 in relation to TDP-43 burden (ρ = −0.73, p = 0.031).
These results highlight that astrocyte populations, and TLE4/CCBE1, display heterogeneous but significant associations between C9orf72 and TDP-43 burden, complementing the strong excitatory neuron correlations and underscoring the interplay between neuronal vulnerability and glial responses in FTLD-TDP.
Code
library(readxl)library(dplyr)library(DT)# ============================================================# LOAD DATA# ============================================================file_path <-"/media/jaumatell/datos/URI/BAYESPRISM_12_3/RESULTS_ORDERED/6. GENES OF INTERST CORRELATION/ALL_genes_correlation.xlsx"filtered <- readxl::read_excel(file_path, sheet =1)# ============================================================# CLEAN COLUMN NAMES IF NEEDED# Some sheets have "NA." or "rho" in first column.# Keep only meaningful columns: Cell, Gene, Spearman, p_value.# ============================================================# Try to detect the first unnamed column (if present)first_col <-colnames(filtered)[1]if (first_col %in%c("NA.", "rho", "rho1", "", NA)) { filtered <- filtered %>%select(-1)}# ============================================================# FILTERABLE HTML TABLE FOR QUARTO# ============================================================datatable( filtered,filter ="top",options =list(scrollX =TRUE,pageLength =25,dom ="frtip"# no download buttons ))